Reclassification Of Patients Research Articles

Reclassification of patients with stage 2 or higher severe aortic valve stenosis based on left atrial reservoir strain

Abstract Introduction Survival following Transcatheter Aortic Valve Replacement (TAVR) is significantly influenced by the extent of extra-valvular cardiac damage at the time of the procedure. Génereux et al. introduced a staging system that classifies patients as stage 2 or higher if they have left atrial (LA) damage, defined as a Left Atrial Volume Index (LAVI) greater than 34mL/m². However, Left Atrial Strain (LAS) may serve as a more advanced method for assessing, LA damage and identifying high-risk patients. Aim This retrospective study aimed to evaluate the contribution of LAS in addition to LAVI in assessing the impairment of LA function in severe aortic valve stenosis (AS). Methods All patients with LAVI >34mL/m² who underwent TAVR between February 2021 and October 2023 were included in the study. Patients with poor quality echocardiographic images, moderate/severe mitral valve stenosis, mitral valve prosthesis, amyloidosis, or atrial fibrillation were excluded. Baseline echocardiographic images were analyzed offline to measure biplane LA volume, LAVI, LAS conduit (cd), LAS contractile (ct), and LAS reservoir (r). Additionally, left ventricular (LV) function was assessed by calculating ejection fraction (EF), global longitudinal strain (GLS), and myocardial work (MW) parameters. A ROC-curve analysis was performed to determine the LA parameter with the best predictive value, for stratification and survival analysis of patients. Results In total, 73 out of 176 AS patients were included in the analysis (39males, 83±5years, AVA 0.7±0.3cm2, MPG 47±15mmHg, LAVI 53±17mL/m²) . The majority of patients were in stage 2 while two were in stage 3 and three were in stage 4. During an average follow-up period of 419±287 days after TAVR, 11 patients died. No correlation was found between LA volume or LAVI and LV function parameters. However LAS parameters showed a significant correlation with EF and MW. Specifically, LASr had a significant correlation with EF (r=0.32), MW index(r=0.41), constructive work (CW, r=0.44), and MW efficiency (r=0.37). In the ROC-curve analysis, LASr demonstrated the highest predictive value (AUC 0.66). Patients with LASr values below the median (18.5%) exhibited significantly poorer long-term survival rates compared to those with LASr values above the median. Patient risk re-stratification based on the median LASr showed improved specificity compared to using LAVI> 34ml/m² as a risk marker (Figure 1). Furthermore, patients with low LASr values also displayed significantly worse values of GLS (-17±8 vs -14±4%, p=0.03), MW index (2598±686 vs 2054±677mmHg%, p=0.02), CW (3135±766 vs 2512±787mmHg%, p=0.02), and MW efficiency (93±5 vs 89±7%, p=0.03). Conclusion The identification of AS patients with LA damage (stage 2) due to LV dysfunction could be enhanced by implementing LASr as a more accurate parameter than LAVI. Additionally, LASr may help in identifying AS patients at risk following TAVR. Figure 1: Survival Analysis

P0389 Cardiovascular risk assessment and ultrasound-assisted reclassification in patients with Inflammatory Bowel Disease (IBD): a single-centre study

Abstract Background Patients with inflammatory bowel disease (IBD) have an increased cardiovascular risk (CVR) and cardiovascular disease (CVD) is the leading cause of mortality in IBD patients. A more in-depth screening of patients has become important with the EMA warning for JAK-inhibitors. The current CV risk stratification algorithms are based on traditional risk factors not considering subclinical atherosclerosis. This study aimed to stratify the CVR of IBD patients according to the European Society of Cardiology (ESC 2021/23) and European Society of Atherosclerosis (EAS), together with the evaluation of the presence of previously subclinical atherosclerosis by carotid ultrasound. Methods Demographic and disease-related data were collected from consecutive IBD patients aged over 40 years, including systolic blood pressure, body mass index (BMI), lipid panel, and cardiovascular comorbidities. Asymptomatic atherosclerotic disease was assessed by carotid ultrasound in order to measure the carotid intima-media thickness (cIMT) and to detect the presence of plaques. CVR was stratified based on the latest guidelines on dyslipidemias (EAS/ESC 2019), cardiovascular prevention (ESC 2021), and the management of cardiovascular disease in patients with diabetes (ESC 2023). Moreover, additional IBD-related parameters potentially associated with an increased CVR were investigated, such as disease activity, current therapies, duration of disease, and extraintestinal manifestations. Results A total of 120 IBD patients were included (UC: 67 patients, CD: 53 patients) Baseline characteristics are presented in Table 1. Patients with UC had significantly higher mean values of total cholesterol (C-TOT) and low-density lipoprotein cholesterol (C-LDL) (p<0.001 and p=0.001 respectively). At baseline, 48% of patients were classified as having intermediate CVR, 34% as high risk, and 18% as very high risk (Table 2). Following carotid ultrasonography, subclinical atherosclerosis was diagnosed in 48.3% of patients. Based on these findings, CVR re-stratification was performed in 21% of patients resulting in 71% of patients with high and very high risk, compared to 50% at baseline. Additional risk factors for an increased CVR identified by multivariate regression analysis were having active disease (p=0.047) and concomitant spondiloathropathies (p=0.03). Conclusion Our study demonstrates that carotid ultrasound contributed to re-classify the CVR in patients who were previously considered to be in lower risk categories confirming that the use of traditional risk scores underestimates CVR in IBD patients. Having active intestinal disease and concomitant spondiloarthritis increases further the CV risk.

Does a Negative Prostate Biopsy Reduce the Risk of Prostate Cancer Reclassification in an Active Surveillance Protocol? An Updated Systematic Review and Meta-Analysis.

To evaluate the association of the negative confirmatory and follow-up biopsy with prostate cancer reclassification in active surveillance protocol. A systematic search was performed in databases, including Scopus, PubMed, Embase, and Web of Science, on June 25th, 2024, to identify relevant studies regarding negative biopsy and reclassification of prostate cancer among men on AS. The patient data including, sample sizes, follow-up duration, the status of performing the confirmatory biopsy, hazard ratio (HR), and 95% confidence intervals (CI) of each reported HR were evaluated in each study. The relationships between negative biopsies and reclassification were assessed using a forest plot. A random-effect meta-analysis was used when high heterogeneity existed among the studies. Otherwise, a fixed-effect meta-analysis was utilized. A p value of less than 0.05 was considered statistically significant. All statistical analyses were performed by using STATA statistical software, version 16. A total of 13 articles were included in the study. These articles were published between 2008 and 2023, with the majority being published in recent years (2020-2023). The included articles evaluated a total of 17,900 patients. Our results regarding reclassification and upgrading are represented according to the confirmatory biopsy and subsequent follow-up biopsies. After a negative confirmatory biopsy, the pooled HR for reclassification was 0.46 (95% CI: 0.38-0.55, p < 0.01). Secondly, the study demonstrated that a decreased chance of cancer upgrading was also connected with negative confirmatory biopsies with a pooled HR of 0.57 (95% CI: 0.45-0.72, p < 0.01). Negative follow-up biopsies were linked to a 55% decrease in the risk of reclassification, according to the pooled HR for reclassification in patients with negative biopsies compared to those with positive biopsies of 0.45 (95% CI: 0.42-0.48, p < 0.01). Also, patients with negative follow-up biopsies had a pooled HR for upgrading of 0.57 (95% CI: 0.48-0.67, p < 0.01), indicating a 43% lower chance of upgrading than in patients with positive biopsies. In active surveillance of PCa patients, a negative confirmatory biopsy decreased the chance of cancer reclassification and upgrading, with the pooled OR 0.46 and 0.57 [p < 0.01], respectively. Also, negative follow-up biopsies were linked to a decreased chance of cancer reclassification and upgrading. Our review recommends extend the follow-up evaluations in PCa patients with negative findings in surveillance biopsy who scheduled for active surveillance.

Host tissue factors predict immune surveillance and therapeutic outcomes in gastric cancer.

The immune composition of solid tumors is typically inferred from biomarkers, such as histologic and molecular classifications, somatic mutational burden, and PD-L1 expression. However, the extent to which these biomarkers predict the immune landscape in gastric adenocarcinoma-an aggressive cancer often linked to chronic inflammation-remains poorly understood. We leveraged high-dimensional spectral cytometry to generate a comprehensive single-cell immune landscape of tumors, normal tissue, and lymph nodes from patients in the Western Hemisphere with gastric adenocarcinoma. The immune composition of gastric tumors could not be predicted by traditional metrics such as tumor histology, molecular classification, mutational burden, or PD-L1 expression via IHC. Instead, our findings revealed that innate immune surveillance within tumors could be anticipated by the immune profile of the normal gastric mucosa. Additionally, distinct T-cell states in the lymph nodes were linked to the accumulation of activated and memory-like CD8+ tumor-infiltrating lymphocytes (TILs). Unbiased re-classification of patients based on tumor-specific immune infiltrate generated four distinct subtypes with varying immune compositions. Tumors with a T-cell-dominant immune subtype, which spanned TCGA molecular subtypes, were exclusively associated with superior responses to immunotherapy. Parallel analysis of metastatic gastric cancer patients treated with immune checkpoint blockade showed that patients who responded to immunotherapy had a pre-treatment tumor composition that corresponded to a T-cell-dominant immune subtype from our analysis. Taken together, this work identifies key host-specific factors associated with intratumoral immune composition in gastric cancer and offers an immunological classification system that can effectively identify patients likely to benefit from immune-based therapies.

ERG and PTEN Role on Active Surveillance for Low-Risk Prostate Cancer in the Multiparametric MRI Era.

Our study aimed to correlate ERG and PTEN expressions in prostate biopsy with multiparametric magnetic resonance imaging PI-RADS score, clinical reclassification, and prognosis of very low-risk prostate cancer (PCa) patients under active surveillance (AS). We evaluated 101 very low-risk PCa patients under AS between 2013 and 2018. They were followed with DRE, PSA, MRI, and re-biopsies every 1-2 years. Per cause biopsy was recommended if PSA > 10 ng/mL, suspicious DRE, or PI-RADS ≥ 4 was present. ERG and PTEN expressions were assessed by immunohistochemistry at biopsy. Reclassification was defined by PSA > 10 ng/mL, re-biopsy with > 3 positive cores, > 50% positive core, Gleason Score (GS) upgrading ≥ 3 + 4 or extreme GS upgrading ≥ 4 + 3. We correlated ERG and PTEN with reclassification, PI-RADS, pathologic outcomes, and biochemical recurrence in patients surgically treated after reclassification. After a 49.2-month follow-up, 80% of patients showed reclassification, and GS upgrading was the most common criterion. Seventy-four out of 81 patients with reclassification underwent local treatment and seven had biochemical recurrence during a mean 39.7-month follow-up. At biopsy, positive ERG expression was found in 39.6% of patients and PTEN loss in 12.6%. PTEN loss was associated with GS upgrading (OR = 9.7, p = 0.011) in univariate analysis. PTEN loss was correlated with GS upgrading; these patients had a 9.7-fold greater chance of upgrading when compared to PTEN-positive patients. ERG-positive was associated with PI-RADS ≥ 4 (OR = 2.8, p = 0.026). At multivariate analysis, PI-RADS ≥ 4 was predictor of GS upgrading (OR = 25.2, p < 0.001); MRI PI-RADS score remained an independent factor for extreme GS upgrading, together with PSAd > 0.15 (OR = 15.1, p = 0.012 and OR = 5.76, p = 0.012, respectively). Neither ERG-positive nor PTEN loss were associated with upgrading during AS. ERG and PTEN biomarkers, despite commonly studied in advanced PCa, have yet no defined role in very low-risk PCa under AS. PI-RADS score was an independent predictor of GS upgrading and extreme upgrading during AS.

Coronary inflammation stratifies risk in patients undergoing coronary CT angiography: the Oxford Risk Factors and Non-Invasive Imaging (ORFAN) study

Abstract Background Patients with chest pain symptoms often undergo coronary CT angiography (CCTA) for the diagnosis of obstructive coronary artery disease (CAD) to guide revascularisation. However, acute cardiac events could occur in the absence of obstructive CAD. Further risk stratification of patients could potentially be useful by quantifying coronary inflammation using the Fat Attenuation Index (FAI) Score, and an artificial intelligence (AI)-assisted prognostic model that captures the inflammatory risk by integrating CCTA-derived metrics (including FAI Score and plaque burden) and the patient’s clinical risk factors. Purpose To evaluate the risk of cardiac events among patients without obstructive CAD, and the prognostic value of integrating coronary inflammation in risk stratifying this patient group. Methods From the Oxford Risk Factors and Non-invasive imaging (ORFAN) study, patients undergoing CCTA in 7 UK Hospitals (n=40,091) were followed up for the incidence of cardiac mortality over a median(IQR) of 2.7(1.4-5.3) years. In a nested cohort of 3,393 patients with long-term follow up, we evaluated the long-term prognostic value of FAI Score and the performance of AI-Risk algorithm over a median(IQR) follow up of 7.7(6.4-9.1) years. Reclassification of risk category from AI-Risk was compared with contemporary clinical risk score (QRISK3). Results Patients without obstructive CAD (n=32,533, 81.1%) accounted for 63.7% of all cardiac deaths (n=1,754) during follow up, highlighting the substantial proportion of cardiac events in absolute terms given a large proportion of patients without obstructive CAD. In the nested cohort with long-term follow up, FAI Score in any of the 3 epicardial coronary arteries was significantly associated with cardiac mortality with or without obstructive CAD. In the whole cohort, the highest quartile of FAI Score in LAD showed 20-times higher risk of cardiac death compared with the lowest quartile (Panel A). Integrating coronary inflammation with clinical risk factors and plaque burden, patients with very-high AI-Risk classification showed 6-fold higher risk of cardiac mortality compared to low/medium risk, with good alignment of the incident predicted events from AI-Risk and observed events. (Panel B) The predicted cardiac mortality from AI-Risk also demonstrated good calibration with the observed events in the whole population. (Panel C) Finally, AI-Risk significantly reclassify the risk above clinical risk factor-based prediction (QRISK3) (Panel D). Conclusion Patients with high coronary inflammation measured by FAI Score showed significantly elevated risk for cardiac mortality. The AI-enabled absolute risk prediction algorithm leads to significant reclassification of patients undergoing routine CCTA, and can be used as a precision medicine tool.

The new FIGO 2023 staging reclassification of patients with FIGO 2009 Stage IVB endometrial cancer correlates to progression-free and overall survival outcomes

ObjectiveThis study aims to determine the oncological outcomes of Stage IVB (FIGO 2009) Endometrial cancer patients and its comparison with the new (FIGO 2023) staging. MethodsA Retrospective analysis was conducted between May 30, 2011, and December 30, 2020 on all patients with stage IVB (FIGO 2009 Staging) endometrial cancer. Overall survival (OS) was the primary outcome. Progression-Free Survival (PFS) and comparison with new staging FIGO 2023 were the secondary outcomes. Kaplan-Meier curves and log-rank tests were used to compare the average OS time and PFS between the groups. ResultsFifty-one patients with Stage IVB endometrial cancer (2009 FIGO Staging) were included. Median age was 68 years. Serous histology was found in 24 (47.1 %) patients. After a median follow-up period of 24 months, median OS was 36 months and median PFS was 15 months. FIGO 2023 staging criteria reclassified the stages of 23 patients (45 %). Patients were restaged into Stage IIIB2 (9.8 %), IVA (5.8 %), IVB (55 %) and IVC (29.4 %). Median OS and PFS were not reached for stages IIIB and IVA, while the median OS and median PFS for stage IVB were 36 months and 18 months, respectively. However, patients with stage IVC had lower median OS and PFS of 10 months and 4 months, respectively. ConclusionThe clinical outcomes of patients with Stage IVB are varied depending mainly on the disease distribution. Patients with abdominal or pelvic disease had better survival outcomes and therefore, needed a different categorisation. Thus, FIGO 2023 Staging considers this varied disease distribution and appears to be a better prognostic indicator for this group.

Prosigna Assay for Treatment Decisions in Early Breast Cancer: A Decision Impact Study.

Introduction: Therapeutic decisions in early breast cancer are based on clinico-pathological features which are subject to intra- and inter-observer variability. This single-center decision impact study aimed to evaluate the effects of the Prosigna assay on physicians' adjuvant treatment choices. Methods: Between 09/2017 and 02/2018, formalin-fixed tumor samples from 52 newly diagnosed, postmenopausal, hormone receptor-positive, HER2-negative breast cancer (T1-T2; pN0-N1a) patients were analyzed. Pre-test clinical judgements and Prosigna test results were compared. Results: The mean age was 59 (42-77). Invasive ductal carcinoma (79.2%), grade 2 (52.8%) and T1c-N0 tumors (43.4%) were represented. There was 40.4% discordance between the pre- and post-test risk of recurrences. No significant change was observed in the clinical intermediate risk category, while there was a net reclassification of low-risk patients into a high Prosigna recurrence risk group. In addition, clinically determined intrinsic subtypes were 34.6% discordant with the Prosigna results, which is largely driven by the reclassification of the luminal A tumors into the Prosigna-assessed luminal B group. Before the Prosigna test, endocrine treatment was the primary choice in 20 patients (39.2%), and chemotherapy was recommended to 31 patients (60.8%). Overall, the Prosigna assay led to a change in treatment choice for one patient. Conclusions: Although conventional risk assessment methods are relatively inexpensive with shorter turnaround times, their accuracy and value for risk reduction are suboptimal. According to our results, the Prosigna assay was found to be a relevant tool for the clinical decision making process. Long-term follow-up of these patients will elucidate the potential benefits of using multigene molecular tests as biomarkers for treatment.

Caucasian validation of downstaging from IIB to IIA in T1N1M0 patients within the 9th edition of the non-small cell lung cancer tumor-node-metastasis staging.

The 9th edition of the lung cancer tumor-node-metastasis (TNM) staging introduced adjustments, including the reclassification of T1N1M0 patients from stage IIB to IIA. This update used data mostly from Asian populations. However, the applicability of these adjustments to Caucasian patients remains uncertain. Stage II non-small cell lung cancer (NSCLC) patients from the Surveillance, Epidemiology, and End Results (SEER) database were included. Kaplan-Meier analysis with log-rank testing compared overall survival (OS) and cancer-specific survival (CSS). Propensity score matching (PSM) balanced baseline characteristics. The least absolute shrinkage and selection operator (LASSO)-based Cox analyses identified prognostic factors. Among 10,470 eligible stage II NSCLC patients (median age: 69 years; male: 53.1%), there were 2736 in stage IIA, 2112 in IIA New, and 5622 in IIB groups. Before PSM, survival outcomes of stage IIA New patients were similar to those of stage IIA patients but better than those of stage IIB. After PSM, stage IIA New and IIB patients showed similar survival rates (OS, p = 0.276; CSS, p = 0.565). Conversely, stage IIA New patients had worse outcomes than stage IIA patients (OS, p < 0.001; CSS, p = 0.005). LASSO-based Cox analyses confirmed stage IIA New patients had inferior prognosis compared to stage IIA patients (OS HR: 1 vs. 1.325, p < 0.001; CSS HR: 1 vs. 1.327, p < 0.001). The downstaging of T1N1M0 patients from stage IIB to IIA in the 9th edition TNM staging remains unverified in Caucasians. Caution is warranted in assessing the staging and prognosis of these individuals. Further validation of our findings is necessary.

EEG and acute confusional state at the emergency department

ObjectivesAcute confusional state (ACS) is a common cause of admission to the emergency department (ED). It can be related to numerous etiologies. Electroencephalography (EEG) can show specific abnormalities in cases of non-convulsive status epilepticus (NCSE), or metabolic or toxic encephalopathy. However, up to 80% of patients with a final diagnosis of NCSE have an ACS initially attributed to another cause. The exact place of EEG in the diagnostic work-up remains unclear. MethodsData of consecutive patients admitted to the ED for an ACS in a two-year period and who were referred for an EEG were collected. The initial working diagnosis was based on medical history, clinical, biological and imaging investigations allowing classification into four diagnostic categories. Comparison to the final diagnosis was performed after EEG recordings (and sometimes additional tests) were performed, which allowed the reclassification of some patients from one category to another. ResultsSeventy-five patients (mean age: 71.1 years) were included with the following suspected diagnoses: seizures for 8 (11%), encephalopathy for 14 (19%), other cause for 34 (45%) and unknown for 19 (25%). EEG was recorded after a mean of 1.5 days after symptom onset, and resulted in the reclassification of patients as follows: seizure for 15 (20%), encephalopathy for 15 (20%), other cause for 29 (39%) and unknown cause for 16 (21%). Moreover, ongoing epileptic activity (NCSE or seizure) and interictal epileptiform activity were found in eight (11%) patients initially diagnosed in another category. DiscussionIn our cohort, EEG was a key examination in the management strategy of ACS in 11% of patients admitted to the ED. It resulted in a diagnosis of epilepsy in these patients admitted with unusual confounding presentations.

ReClassification of Patients with Ambiguous CA125 for Optimised Pre-Surgical Triage.

Pre-surgical clinical assessment of an adnexal mass is a complex process, and ideally requires accurate and rapid identification of disease status. Gold standard biomarker CA125 is extensively used off-label for this purpose; however its performance is typically inadequate, particularly for the detection of early stage disease and discrimination between benign versus malignant status. We recently described a multi-marker panel (MMP) and associated risk index for the differentiation of benign from malignant ovarian disease. In this study we applied a net reclassification approach to assess the use of MMP index to rescue those cases where low CA125 incorrectly excludes cancer diagnoses, or where benign disease is incorrectly assessed as "high risk" due to elevated CA125. Reclassification of such patients is of significant value to assist in the timely and accurate referral for patients where CA125 titer is uninformative.

Are the Chicago 3.0 manometric diagnostics consistent with Chicago 4.0?

There is little information on the degree of concordance between the results obtained using the Chicago 3.0 (CCv3.0) and Chicago 4.0 (CCv4.0) protocols to interpret high-resolution manometry (HRM) seeking to determine the value provided by the new swallowing maneuvers included in the last protocol. This is a study of diagnostic tests, evaluating concordance by consistency between the results obtained by the CCv3.0 and CCv4.0 protocols, in patients undergoing HRM. Concordance was assessed with the kappa test. Bland-Altman scatter plots, and Lin's correlation-concordance coefficient (CCC) were used to assess the agreement between IRP measured with swallows in the supine and seated position or with solid swallows. One hundred thirty-two patients were included (65% women, age 53 ± 17years). The most frequent HRM indication was dysphagia (46.1%). Type I was the most common type of gastroesophageal junction. The most frequent CCv4.0 diagnoses were normal esophageal motility (68.9%), achalasia (15.5%), and ineffective esophageal motility (IEM; 5.3%). The agreement between the results was substantial (Kappa 0.77 ± 0.05), with a total agreement of 87.9%. Diagnostic reclassification occurred in 12.1%, from IEM in CCv3.0 to normal esophageal motility in CCv4.0. Similarly, there was a high level of agreement between the IRP measured in the supine compared to the seated position (CCC0.92) and with solid swallows (CCC0.96). In conclusion, the CCv4.0 protocol presents a high concordance compared to CCv3.0. In the majority of manometric diagnoses there is no reclassification of patients with provocation tests. However, the more restrictive criteria of CCv4.0 achieve a better reclassification of patients with IEM.

OP79 Gene Expression Profiling In The Diagnosis Of Aggressive Large B Cell Lymphoma: An Early Exploratory Economic Evaluation

IntroductionThe addition of gene expression profiles (GEP) to the current clinicopathological diagnosis of aggressive large B cell lymphomas may lead to the reclassification of patients, treatment changes and improved outcomes. A GEP test is in development using TempoSeq technology to distinguish Burkitt Lymphoma (BL) and Primary Mediastinal Large B Cell lymphoma (PMBCL) from Diffuse Large B Cell Lymphoma (DLBCL). This study aims to inform developers about the potential impact of the test on costs and health outcomes, and pricing and evidence generation strategies.MethodsDecision models compared current diagnosis with current plus GEP signatures over a lifetime horizon using a UK health and social care perspective. Inputs were taken from the literature and based on assumptions. Threshold estimates were made of the maximum price of the test and impact of incorrect disease classification using a threshold of GDP30,000 (USD37,155) per Quality Adjusted Life year (QALY). One way sensitivity analysis was conducted.ResultsAt base case values the BL signature delivers incremental QALYs of 0.0249 at an additional cost per patient of GBP508 (USD629). This results in a net monetary benefit (NMB) of GBP239 (USD296). The PMBCL signature delivers 0.0011 QALYs, a cost saving of GBP202 (USD250) and an NMB of GBP236 (USD292). The maximum threshold price for a combined test to be cost effective is GBP776 (USD961) (base case GBP400 (USD495)). Results are sensitive to cost differences in first line treatments and impact of false diagnoses.ConclusionsA combined test could be cost-effective in a UK context at a price around GBP750 (USD929). The developers can use this estimate to inform return on investment calculations. The number of patients who were reclassified as a result of the addition of GEP in our model was taken from small retrospective studies and the impact of false diagnoses was based on limited evidence. If the developers choose to proceed with the development, these aspects should be incorporated in evidence generation strategies.

Neuro-oncology Treatment Strategies for Primary Glial Tumors.

Primary brain tumors underwent reclassification in the 2021 World Health Organization update, relying on molecular findings (especially isocitrate dehydrogenase mutations and chromosomal changes in 1p, 19q, gain of chromosome 7 and loss of chromosome 10). Newer entities have also been described including histone 3 mutant midline gliomas. These updated pathologic classifications improve prognostication and reliable diagnosis, but may confuse interpretation of prior clinical trials and require reclassification of patients diagnosed in the past. For patients over seventy, multiple studies have now confirmed the utility of shorter courses of radiation, and the risk of post-operative delirium. Ongoing studies are comparing proton to photon radiation. Long term follow up of prior clinical trials have confirmed the roles and length of chemotherapy (mainly temozolomide) in different tumors, as well as the wearable novottf device. New oral isocitrate dehydrogenase inhibitors have also shown efficacy in clinical trials.

Adding a Gene Expression Profile Test to Aid Differential Diagnosis and Treatment in Aggressive Large B-Cell Lymphoma: An Early Exploratory Economic Evaluation.

Adding gene expression profiles (GEPs) to the current diagnostic work-up of aggressive large B-cell lymphomas may lead to the reclassification of patients, treatment changes and improved outcomes. A GEP test is in development using TempO-Seq® technology to distinguish Burkitt lymphoma (BL) and primary mediastinal large B-cell lymphoma (PMBCL) from diffuse large B-cell lymphoma (DLBCL), and to classify patients with DLBLC and to predict the benefit of (e.g.) adding bortezomib to R-CHOP therapy (RB-CHOP). This study aims to estimate the potential impact of a GEP test on costs and health outcomes to inform pricing and evidence generation strategies. Three decision models were developed comparing diagnostic strategies with and without GEP signatures over a lifetime horizon using a UK health and social care perspective. Inputs were taken from a recent clinical trial, literature and expert opinion. We estimated the maximum price of the test using a threshold of Great Britain Pound (GBP) 30,000 per quality-adjusted life-year (QALY). Sensitivity analyses were conducted. The estimated maximum threshold price for a combined test to be cost effective is GBP 15,352. At base-case values, the BL signature delivers QALY gains of 0.054 at an additional cost of GBP 275. This results in a net monetary benefit at a threshold of GBP 30,000 per QALY of GBP 1345. For PMBCL, the QALY gain was 0.0011 at a cost saving of GBP 406 and the net monetary benefit was GBP 437. The hazard ratio for the impact of treating BL less intensively must be at least 1.2 for a positive net monetary benefit. For identifying patients with the DLBCL subtype responsive to bortezomib, QALY gain was 0.2465 at a cost saving of GBP 6175, resulting in a net monetary benefit of GBP 13,570. In a probabilistic sensitivity analysis using 1000 simulations, a testing strategy was superior to a treat all with R-CHOP strategy in 81% of the simulations and with a cost saving in 92% assuming a cost price of zero. Our estimates show that the combined test has a high probability of being cost effective. There is good quality evidence for the benefit of subtyping DLBCL but the evidence on the number of patients reclassified to or from BL and PMBCL and the impact of a more precise diagnosis and the cost of treatment is weak. The developers can use the price estimate to inform a return on investment calculations. Evidence will be required of how well the TempO-Seq® technology performs compared to the testing GEP technology used for subtyping in the recent clinical trial. For BL and PMBCL elements of the test, evidence would be required of the number of patients reclassified and improved costing information would be useful. The diagnostic and therapeutic environment in haematological malignancies is fast moving, which increases the risk for developers of diagnostic tests.

Left ventricular ejection fraction digit bias and reclassification of heart failure with mildly reduced vs reduced ejection fraction based on the 2021 definition and classification of heart failure

Aims were to evaluate (1) reclassification of patients from heart failure with mildly reduced (HFmrEF) to reduced (HFrEF) ejection fraction when an EF=40% was considered as HFrEF, (2) role of EF digit bias, ie, EF reporting favouring 5% increments; (3) outcomes in relation to missing and biased EF reports, in a large multinational HF registry. Of 25,154 patients in the European Society of Cardiology (ESC) HF Long-Term registry, 17% had missing EF and of those with available EF, 24% had HFpEF (EF≥50%), 21% HFmrEF (40%-49%) and 55% HFrEF (<40%) according to the 2016 ESC guidelines´ classification. EF was "exactly" 40% in 7%, leading to reclassifying 34% of the HFmrEF population defined as EF=40% to 49% to HFrEF when applying the 2021 ESC Guidelines classification (14% had HFmrEF as EF=41% to 49% and 62% had HFrEF as EF≤40%). EF was reported as a value ending with 0 or 5 in ∼37% of the population. Such potential digit bias was associated with more missing values for other characteristics and higher risk of all-cause death and HF hospitalization. Patients with missing EF had higher risk of all-cause and CV mortality, and HF hospitalization compared to those with recorded EF. Many patients had reported EF=40%. This led to substantial reclassification of EF from old HFmrEF (40%-49%) to new HFrEF (≤40%). There was considerable digit bias in EF reporting and missing EF reporting, which appeared to occur not at random and may reflect less rigorous overall care and worse outcomes.

Abstract 16148: Calculating Indexed Aortic Root Diameters With Ideal Body Weight Leads to Significant Reclassification in Overweight and Obese Patients

Introduction: Indexed Aortic root diameter (AoR diam) measured by transthoracic echocardiography (TTE) using body surface area (BSA) is important in children, adolescents, and small adults in whom non-indexed values may under detect dilation. However, indexed AoR diam may lead to misleading results in obese individuals as the AoR diam does not increase in proportion to body weight. Hypothesis: We hypothesize that using ideal body weight (IBW, using the Devine formula) in place of actual weight in BSA calculation reclassifies a significant proportion of indexed AoR diam in overweight and obese patients. Methods: We performed a retrospective review of all patients with a TTE at Tufts Medical Center in 2022 and Ao root diam &gt;4 cm for men and &gt;3.6 cm for women. We excluded patients &lt; 20 years old and those with inadequate TTE images or missing aortic measurements. TTE data and baseline characteristics were recorded. Indexed AoR diam was calculated using both actual and ideal body weights. The thresholds for for mildly, moderately, and severely dilated indexed AoR were ≥2.2, ≥2.4, and ≥2.6 in men, and ≥2.3, ≥2.4, and ≥2.6 in women, respectively. Results: 456 patients (400 males, 56 females) met our inclusion criteria, with a subset of 331 patients (72.6%) with BMI ≥25. When ideal body weight was used for indexing AoR diam, 58.7% of patients initially classified as having 'normal' indexed AoR diam were reclassified as at least 'mildly dilated' (p&lt;0.001). Patients with a BMI ≥25 were more often reclassified as at least ‘mildly dilated’ compared to those with lower BMI (64.6% vs. 13.3%, p&lt;0.001). In stratified analysis, upward reclassification occurred in 31.9% of patients with 'mildly dilated' AoR diam (45.8% in BMI ≥25) and 35.2% of patients with 'moderately dilated' AoR diam (80% in BMI ≥25). Conclusions: The use of ideal body weight instead of actual body weight for indexing AoR diam changes risk-stratification in over half of the patients with an abnormal AoR. This is more pronounced in patients with a BMI ≥25 and may have significant management implications. Further studies are needed to investigate if the use of actual weight in Ao root indexing systematically underestimates Ao root dilation in overweight and obese patients and if the use of IBW can improve risk assessment.

Feature-Tracking Strain Parameters Differ Between Highly Accelerated and Conventional Acquisitions: A Multisoftware Assessment.

Cardiac magnetic resonance imaging protocols have been adapted to fit the needs for faster, more efficient acquisitions, resulting in the development of highly accelerated, compressed sensing-based (CS) sequences. The aim of this study was to evaluate intersoftware and interacquisition differences for postprocessing software applied to both CS and conventional cine sequences. A total of 106 individuals (66 healthy volunteers, 40 patients with dilated cardiomyopathy, 51% female, 38±17y) underwent cardiac magnetic resonance at 3T with retrospectively gated conventional cine and CS sequences. Postprocessing was performed using 2 commercially available software solutions and 1 research prototype from 3 different developers. The agreement of clinical and feature-tracking strain parameters between software solutions and acquisition types was assessed by Bland-Altmann analyses and intraclass correlation coefficients. Differences between softwares and acquisitions were assessed using Kruskal-Wallis analysis of variances. In addition, receiver operating characteristic curve-derived cutoffs were used to evaluate whether sequence-specific cutoffs influence disease classification. There were significant intersoftware ( P <0.002 for all except LV end-diastolic volume per body surface area) and interacquisition differences ( P <0.02 for all except end-diastolic volume per body surface area from Neosoft, left ventricular mass per body surface area from cvi42 and TrufiStrain and global circumferential strain from Neosoft). However, the intraclass correlation coefficients between acquisitions were strong-to-excellent for all parameters (all ≥0.81). In comparing individual softwares to a pooled mean, Bland-Altmann analyses revealed smaller magnitudes of bias for cine acquisition than for CS acquisition. In addition, the application of conventional cutoffs to CS measurements did not result in the false reclassification of patients. Significantly lower magnitudes of strain and volumetric parameters were observed in retrospectively gated CS acquisitions, despite strong-to-excellent agreement amongst software solutions and acquisition types. It remains important to be aware of the acquisition type in the context of follow-up examinations, where different cutoffs might lead to misclassifications.

Performance of the Molecular International Prognostic Scoring System (IPSS-M) in Hypomethylating Agent-Treated Patients with Myelodysplastic Syndromes

Background: Patients with myelodysplastic syndromes (MDS) undergo risk stratification with various prognostication tools, such as the International Prognostic Scoring System (IPSS) and Revised IPSS (IPSS-R). Recently, the Molecular IPSS (IPSS-M) was developed incorporating genomic data in addition to clinical and cytogenetic characteristics. Though IPSS-M has been shown to improve prognostication in all MDS patients at baseline, its utility in specifically patients undergoing hypomethylating agent (HMA) therapy remains unknown. Here, we assess the efficacy of IPSS-M in HMA-treated patients with MDS. Methods: We retrospectively evaluated all untreated patients with MDS seen at a single tertiary cancer center from July 2017 to July 2021 and identified those who later received HMA therapy. Patient characteristics and bone marrow (BM) data, including morphology, cytogenetics, and mutations, were assessed at diagnosis. Genomic DNA was extracted from whole BM aspirate samples and subject to 81-gene target PCR-based sequencing using a next-generation sequencing platform. Survival data was updated in July 2023. Results: Out of 799 untreated MDS patients, 455 patients (57%) eventually underwent treatment with HMA. At diagnosis, the median age was 69 (range: 22-90) with 289 (64%) male patients. Patients were generally high risk, with therapy-related MDS in 160 (35%), complex cytogenetics in 167 (37%), and TP53 mutations in 168 (37%). By IPSS-R, 259 patients (58%) had high- or very high-risk disease, and 340 patients (75%) had higher-risk disease (moderate high-, high-, and very high-risk) by IPSS-M. A total of 291 patients (64%) were treated with HMA monotherapy, and lower-risk MDS patients received more cycles of HMA (p &amp;lt; 0.001). By IPSS-R, the median overall survival was 60.0 months (95% CI: 46.0, not estimable (NE)) in very low-, 87.4 months (95% CI: 59.9, NE) in low-, 36.2 months (95% CI: 30.0, 58.1) in intermediate-, 23.7 months (95% CI: 19.6, 34.8), in high-, and 12.8 months (95% CI: 11.0, 16.7) in very high-risk patients (p &amp;lt; 0.0001) with a concordance index of 0.669. Figure 1 depicts the reclassification of patients between IPSS-R and IPSS-M. Risk stratification by IPSS-M (Figure 2) provided similar results: not reached (95% CI: 56.8, NE) in very low-, 60.0 months (95% CI: 49.8, NE) in low-, 40.8 months (95% CI: 22.8, NE) in moderate low-, 44.2 months (95% CI: 27.8, NE) in moderate high-, 33.4 months (95% CI: 22.8, 44.5) in high-, and 16.6 months (95% CI: 13.8, 19.4) in very high-risk patients (p &amp;lt; 0.0001). The concordance index of IPSS-M in all HMA-treated MDS patients was 0.648. When analyzing patients with MDS who were more likely to undergo HMA as per standard-of-care treatment (those with IPSS-M moderate low-, moderate high-, high-, and very high-risk disease), the IPSS-M remained statistically significant (p &amp;lt; 0.0001) though less discerning in the patients with moderate-risk MDS, as seen by the concordance index of 0.620. Conclusions: In this group of MDS patients treated with HMA, the IPSS-M did not provide additional prognostic power over the IPSS-R though median overall survival remained inversely proportional to IPSS-M risk category. Concordance indices for survival remained below 0.7, likely due to the overlapping curves in moderate-risk patients by IPSS-M. Further development and validation of prognostic scoring systems in patients treated with HMA are warranted.

Cardiovascular risk assessment in patients with antiphospholipid syndrome: a cross-sectional performance analysis of nine clinical risk prediction tools

ObjectivesThis study aimed to assess the performance of cardiovascular risk (CVR) prediction models reported by European Alliance of Associations for Rheumatology and European Society of Cardiology recommendations to identify high-atherosclerotic...